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BACKGROUND Anthracycline-based chemotherapy has been mainstay of adjuvant breast cancer therapy for decades. Although effective, anthracyclines place long-term breast cancer survivors at risk of late effects, such as reduced cardiorespiratory fitness and increased risk of cardiovascular disease. Previous research has shown beneficial effects of exercise training on cardiorespiratory fitness, but the effects of exercise on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes in long-term survivors are less clear. Whether previous exposure to breast cancer therapy modulates the effects of exercise is also unknown. OBJECTIVE The primary aim of the CAUSE (Cardiovascular Survivors Exercise) trial is to examine the effect of aerobic exercise on cardiorespiratory fitness in anthracycline-treated long-term breast cancer survivors. Secondary aims are to examine effects of exercise training on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes, and to compare baseline values and effects of exercise training between similar-aged women with and those without prior breast cancer. A third aim is to examine the 24-month postintervention effects of aerobic exercise on primary and secondary outcomes. METHODS The CAUSE trial is a 2-armed randomized controlled trial, where 140 long-term breast cancer survivors, 8-12 years post diagnosis, are assigned to a 5-month nonlinear aerobic exercise program with 3 weekly sessions or to standard care. Seventy similar-aged women with no history of cancer will undergo the same exercise program. Cardiorespiratory fitness measured as peak oxygen consumption (VO2peak), limiting factors for VO2peak (eg, cardiac function, pulmonary function, hemoglobin mass, blood volume, and skeletal muscle characteristics), cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia, obesity, physical activity level, and smoking status), and patient-reported outcomes (eg, body image, fatigue, mental health, and health-related quality of life) will be assessed at baseline, post intervention, and 24 months post intervention. RESULTS A total of 209 patients were included from October 2020 to August 2022, and postintervention assessments were completed in January 2023. The 24-month follow-up will be completed in February 2025. CONCLUSIONS The findings from the CAUSE trial will provide novel scientific understanding of the potential benefits of exercise training in long-term breast cancer survivors. CLINICALTRIAL ClinicalTrials.gov NCT04307407; https://clinicaltrials.gov/ct2/show/NCT04307407 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/45244

This document describes the contribution of clinical criteria to the interpretation of genetic variants using heritable Mendelian cardiomyopathies as an example. The aim is to assist cardiologists in defining the clinical contribution to a genetic diagnosis and the interpretation of molecular genetic reports. The identification of a genetic variant of unknown or uncertain significance is a limitation of genetic testing, but current guidelines for the interpretation of genetic variants include essential contributions from clinical family screening that can establish a de novo assignment of the variant or its segregation with the phenotype in the family. A partnership between clinicians and patients helps to solve major uncertainties and provides reliable and clinically actionable information.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by the Norwegian Research Council [203489/030] onbehalf Department of Cardiology, Research group for genetic cardiac diseases and sudden cardiac death, Oslo University Hospital, Rikshospitalet, Oslo, Norwa Background Lamin A/C disease is an inheritable cardiomyopathy characterized by conduction abnormalities, ventricular arrhythmias and end stage heart failure with complete age-related penetrance. Purpose To assess left ventricular structural and functional progression in patients with lamin A/C cardiomyopathy. Methods We included and followed consecutive lamin A/C genotype positive patients with clinical examination and echocardiography at every visit. We evaluated progression of left- ventricular size and function by mixed model statistics. Results We included 101 consecutive lamin A/C genotype positive patients (age 44 [29-54] years, 39% probands, 51%female) with 576 echocardiographic exams during 4.9 (IQR 2.5-8.1) years of follow-up. LV ejection fraction (LVEF) declined from 50 ± 12% to 47 ± 13%, p 58 years, we observed a decline in LV volumes 148, SE 9 ml to 140, SE 9 ml p < 0.001 (rate -2.7 ml/year) towards end stage heart failure. Conclusions LVEF deteriorated, while LV size remained unchanged during 4.9 years of follow-up in patients with lamin A/C cardiomyopathy. In patients Abstract Figure.

En rekke genetiske skjelettmuskeldystrofier er assosiert med kardiomyopati med hjertesviktutvikling og risiko for plutselig død. Grad av kardial affeksjon er ikke nødvendigvis relatert til grad av skjelettmuskelaffeksjon, og plutselig hjertedød kan være første tegn på kardiomyopati. For å iverksette behandling og forebyggende tiltak mot livstruende kardiale hendelser er det nødvendig med økt oppmerksomhet blant allmennleger og spesialister.

CPVT (catecholaminergic polymorphic ventricular tachycardia) is a condition characterized by syncopes and cardiac arrest that was first described in 1975. CPVT has later been classified as a genetic disease with a great risk for life-threatening arrhythmias that are mainly caused by mutations in the ryanodine receptor 2 gene. Starting with a case report, we present an overview of CPVT.The literature reviewed was identified through a non-systematic search in PubMed.Diagnosing CPVT may be difficult, as resting ECG is normal and the syncopes may be misdiagnosed as epilepsy. Information about syncopes related to physical or emotional stress and occurrence of unexplained syncopes or cardiac arrest among family members, is important in the diagnostic evaluation. An exercise stress test often reveals the classical pattern of ventricular arrhythmias at heart rates above 100 beats/min. The diagnosis can be confirmed by genetic testing. By beta-blocker treatment and, if necessary, an ICD (implantable cardioverter defibrillator) the prognosis can be improved.CPVT is a serious disease with a poor prognosis when left untreated. It is a rare but important differential diagnosis in young individuals with syncopes or cardiac arrest. Genetic screening of relatives has made it possible to identify mutation carriers in affected families in order to provide them with preventive therapy.

Long QT syndrome is characterised by inherited long QT interval on the ECG and increased risk for syncope and sudden death caused by arrhythmias. For Romano-Ward syndrome and Jervell and Lange-Nielsen syndrome DNA based diagnostics are available.This paper is a summary of our experience with DNA-based diagnostics of LQTS since the autumn of 2003. The diagnostic analyses are performed by sequencing the exons of five genes, KCNQ1, HERG, SCN5A, minK and MiRP1.As of mid-January 2005, 56 probands with long QT syndrome have been referred for genetic testing. We have identified an underlying mutation in 64% of the patients. Mutations in the KCNQ1 gene are most frequent in Norwegian long QT syndrome patients, as 61% of the patients have their mutation in this gene. The detection of a mutation in the probands has led to genetic testing of 215 relatives; 99 out of these are heterozygous for the mutation present in the family. Heterozygous patients have been referred to a cardiologist. Of the 43 that have been referred to follow up at the department of cardiology at Rikshospitalet, 35 have started treatment with beta blockers to reduce the risk of arrhythmias. Thus, DNA-based diagnostics has clinical significance leading to prophylactic treatment of long QT syndrome patients. Compared to evaluation of ECG, which is negative in 30% of mutation carriers, the sensitivity of DNA-based diagnostics of relatives of probands with a known mutation, is close to 1.

Inherited arrhythmogenic disorders are a group of genetically determined diseases characterised by ventricular tachyarrhythmias sometimes leading to sudden death. The molecular bases of these disorders are mutations in genes coding for various cardiac ion channels. The most common cardiac ion channel disease is the long QT syndrome. This syndrome is rare, but probably more common in Norway than previously expected. We have recently started genetic testing for cardiac ion channel disorders at Rikshospitalet University Hospital in Oslo. This review describes the current understanding of the etiology, prognosis and management of cardiac ion channel disorders, based on literature and our own clinical experience.Cardiac ion channel disorders may lead to sudden cardiac death. Prophylactic and life-saving therapies are available for many of these disorders. Therapy and risk stratification depend on the clinical presentation, the ECG pattern, and which gene is mutated. Genetic testing offers the opportunity to exclude individual family members as mutation carriers.

Myocarditis is defined as an inflammatory or infectious disease of the myocardium causing damage through production of a toxin or by immunologically mediated destruction. A rare type is idiopathic giant cell myocarditis.We present data from Rikshospitalet University Hospital in Norway, with two case reports and a discussion of the diagnostics and treatments currently available. The investigation is retrospective and includes 11 patients, two women and nine men with histologically verified idiopathic giant cell myocarditis.Median age was 46; four patients had autoimmune co-morbidity. The major onset symptom was rapid progressive heart failure; 64% had concomitant ventricular arrhythmias. Five patients received immunosuppressives in addition to conventional treatment for heart failure. Eight underwent cardiac transplantation and two patients had recurrence of idiopathic giant cell myocarditis in the graft. Mean interval from time of diagnosis to death or cardiac transplantation was six months.Idiopathic giant cell myocarditis is a rare inflammatory disease of the myocardium that often affects previously healthy young adults. Co-morbidity with autoimmune disorders has been reported. Idiopathic giant cell myocarditis is characterised by a history of rapid progression of severe heart failure associated with refractory ventricular arrhythmias. The diagnosis is made by endomyocardial biopsy. Treatment includes immunosuppressives, and the indication for cardiac transplantation should be evaluated early, as one should bear in mind an increased risk of recurrence in the graft.